6-89182042-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002042.5(GABRR1):c.812T>C(p.Leu271Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002042.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRR1 | NM_002042.5 | c.812T>C | p.Leu271Pro | missense_variant | 8/10 | ENST00000454853.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRR1 | ENST00000454853.7 | c.812T>C | p.Leu271Pro | missense_variant | 8/10 | 1 | NM_002042.5 | P1 | |
GABRR1 | ENST00000435811.5 | c.761T>C | p.Leu254Pro | missense_variant | 7/9 | 2 | |||
GABRR1 | ENST00000369451.7 | c.551T>C | p.Leu184Pro | missense_variant | 10/12 | 5 | |||
GABRR1 | ENST00000457434.1 | c.*773T>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251444Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135890
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727230
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.812T>C (p.L271P) alteration is located in exon 8 (coding exon 8) of the GABRR1 gene. This alteration results from a T to C substitution at nucleotide position 812, causing the leucine (L) at amino acid position 271 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at